Tamoxifen May Slow Cognitive Decline

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This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

SAN DIEGO -- Tamoxifen and other selective estrogen receptor modulators may help stay cognitive decline in postmenopausal women, particularly those at risk for Alzheimer's disease, researchers reported here.

Compared with placebo, postmenopausal women who received tamoxifen had significantly less impaired -- and in some cases improved -- episodic memory in an experiment where memory was impaired through delivery of cholinergic antagonists, according to Paul Newhouse, MD, of the Vanderbilt School of Medicine in Nashville, Tenn., and colleagues.

The effect of tamoxifen on simulated cognitive decline was particularly marked among participants whose risk for developing Alzheimer's disease was increased by the presence of the APOE4 gene (P<0.001), Newhouse said during an oral presentation at the Society for Neurology meeting.

The researchers studied whether tamoxifen can produce positive effects of cholinergic-related cognition in a population of 21 postmenopausal women who were otherwise healthy, had not received hormone replacement therapy within a year of the study baseline, and had no history of breast cancer or cognitive impairment.

Newhouse noted that his past research has shown that age-related cognitive changes involve cholinergic function and dysfunction, and that "estrogen effects on cognitive processes after menopause are mediated partially through salutary effects on brain cholinergic systems."

Participants were randomized to 20 mg of tamoxifen or placebo over 3 months and then participated in anti-cholinergic drug challenges with comprehensive cognitive testing, which included receipt of mecamylamine and scopolamine followed by attention and psychomotor function tasks, verbal episodic memory tests, and a virtual water navigation task. The participants then had a 3-month washout followed by a crossover re-trial.

Drug treatment was associated with "partially or completely reversed effects of cholinergic antagonists on episodic memory," and "lessened impairment after cholinergic antagonists" during the Virtual Morris Watermaze task.

Women treated with tamoxifen for 3 months "showed significantly smaller impairments on attention, verbal memory, and spatial navigation than when they had taken 3 months of placebo," they wrote in an accompanying outline of the study.

Women with the APOE4 genotype who received tamoxifen also had markedly improved time in the water maze versus those treated with placebo or who were negative for the genotype; that same group also did better on the number of words recalled.

Newhouse added that these findings may open new research avenues into new selective estrogen receptor modulators with the same clinical benefits but without the adverse events of estradiol.

He also added that follow-up research will look at which populations of women have greater benefit from estrogen stimulation.

He cautioned that his study was limited by its experimental design with an artificial model of induced cognitive decline.

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